Induction of Petite Colonies in Candida glabrate via Rose Bengal-Mediated Photodynamic Therapy.

Facing a 40% mortality rate in candidemia patients, drug-resistant Candida and their petite mutants remain a major treatment challenge. Antimicrobial photodynamic therapy (aPDT) targets multiple fungal structures, unlike antibiotics/antifungals, potentially thwarting resistance. Traditional methods for inducing petite colonies rely on ethidium bromide or fluconazole, which can influence drug susceptibility and stress responses. This study investigated the application of green light (peak 520 nm) and rose bengal (RB) photosensitizer to combat a drug-resistant Candida glabrata isolate. The findings revealed that aPDT treatment significantly inhibited cell growth (≥99.9% reduction) and effectively induced petite colony formation, as evidenced by reduced size and loss of mitochondrial redox indicator staining. This study provides initial evidence that aPDT can induce petite colonies in a multidrug-resistant C. glabrata strain in vitro, offering a potentially transformative approach for combating resistant fungal infections.

TIMP3/Wnt axis regulates gliosis of Müller glia.

BACKGROUND: Previous studies have confirmed the expression of tissue inhibitor of metalloproteinase-3 (TIMP3) in Müller glia (MG). However, the role of TIMP3 in MG remains unknown. METHODS: A mouse model of laser-induced retinal damage and gliosis was generated using wild-type C57BL/6 mice. TIMP3 and associated proteins were detected using Western blotting and immunofluorescence microscopy. RNA sequencing (GSE132140) of mouse laser-induced gliosis was utilized for pathway analysis. TIMP3 overexpression was induced in human MG. Human vitreous samples were obtained from patients with proliferative diabetic retinopathy (PDR) and healthy controls for protein analysis. RESULTS: TIMP3 levels increased in mouse eyes after laser damage. Morphology and spatial location of TIMP3 indicated its presence in MG. TIMP3-overexpressing MG showed increased cellular proliferation, migration, and cell nuclei size, suggesting TIMP3-induced gliosis for retinal repair. Glial fibrillary acidic protein (GFAP) and vimentin levels were elevated in TIMP3-overexpressing MG and laser-damaged mouse retinas. RNA sequencing and Western blotting suggested a role for ß-catenin in mediating TIMP3 effects on the retina. Human vitreous samples from patients with PDR showed a positive correlation between TIMP3 and GFAP levels, both of which were elevated in patients with PDR. CONCLUSIONS: TIMP3 is associated with MG gliosis to enhance the repair ability of damaged retinas and is mediated by the canonical Wnt/ß-catenin. Changes in TIMP3 could potentially be used to control gliosis in a range of retinal diseases However, given the multifaceted nature of TIMP3, care must be taken when developing treatments that aim solely to boost the function of TIMP3. FUNDING: National Cheng Kung University Hospital, Taiwan (NCKUH-10604009 and NCKUH-11202007); the Ministry of Science and Technology (MOST 110-2314-B-006-086-MY3).

Diagnosis, Treatment, and Prevention of Noninfectious Acute Anterior Uveitis with or without Human Leukocyte Antigen B27 in Adults - Expert Consensus in Taiwan.

BACKGROUND: Anterior uveitis is the most common anatomical type of uveitis. Patients with noninfectious anterior uveitis may develop various ocular complications and eventually visual impairment. Appropriately differentiating the etiologies can help clinicians to predict the outcome, arrange clinical follow-up, and decide the treatment or prevention strategy. Adequate treatment and effective prevention strategies can reduce the frequency of recurrence and the risk of developing complications. Human leukocyte antigen (HLA)-B27 is the most common positive finding in patients with noninfectious AAU in many countries including Taiwan. PURPOSE: To report a consensus from experienced uveitis specialists and rheumatologists was made in Taiwan. METHODS: A panel of nine ophthalmologists from nine different referral centers with expertise in the management of uveitis and an experienced rheumatologist was held on January 16, 2022. A comprehensive literature review was performed. Differential diagnoses for etiologies, general treatments, and prevention strategies were discussed. Each statement in the consensus was made only if more than 70% of the experts agreed. RESULTS: A flow chart and seven statements regarding the differential diagnoses for etiologies, treatments and preventions, and co-management with rheumatologists were included in the consensus. CONCLUSIONS: This article discusses the general diagnosis, treatment, and prevention of noninfectious acute anterior uveitis, with or without HLA-B27, in adults for general ophthalmologists to improve overall outcomes of these patients.

Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Trends in diabetic eye disorders and associated comorbidities in Taiwan: a 10-year nationwide population-based cohort study.

BACKGROUND/AIMS: In-depth analysis is needed to investigate trends in diabetic retinopathy (DR), diabetic macular oedema (DME) and associated comorbidities in patients with type 2 diabetes mellitus (T2DM) so that we can better understand their prevalence and incidence. METHODS: A retrospective population-based study was conducted using data from Taiwan's National Health Insurance Research Database from 2005 to 2015, and T2DM, DR and associated comorbidities were identified based on diagnostic codes. We used a standardised incidence rate with age and sex adjustment to estimate the prevalence and incidence of DR, proliferative DR (PDR), advanced PDR (aPDR) and DME, while the difference in each study period was calculated as the annual percentage change. We used the absolute standardised difference to analyse changes in related comorbidities in different periods. RESULTS: The population of patients with DM increased over 50% between 2005 and 2015, while the prevalence and incidence of DR decreased, as did the incidence of PDR and aPDR. However, the prevalence and incidence of DME increased over the course of 10 years, with an upward trend in all forms of DR. The percentage of patients with hyperlipidaemia in DME and all DR increased, and the percentage of patients with end-stage renal disease (ESRD) was also elevated in DME. CONCLUSION: The prevalence and incidence of DR, PDR and aPDR decreased with time in patientsT2DM, while the ratio of DME increased gradually. The incidence of hyperlipidaemia also increased in all forms of diabetic eye disorders, while ESRD increased solely in DME.

Dilated choroidal vascular channels in pachychoroid neovasculopathy.

BACKGROUND: To elucidate the pattern of the choroidal vasculature in exudative pachychoroid neovasculopathy (PNV) and its correlation with the clinical course and treatment outcomes. METHODS: The retrospective study included consecutive patients in National Taiwan University Hospital between 2014 and 2020 who fulfilled the criteria for exudative PNV defined as active type 1 macular neovascularization (MNV) on optical coherence tomography angiography (OCTA) and with leakage on fluorescein angiography (FA) or indocyanine green angiography (ICGA) associated with pachychoroid features. The corrected distance visual acuity (CDVA), FA, ICGA, and OCT images obtained by Optovue (Optovue Inc, Freemont CA, USA) spectral domain OCT were evaluated at baseline and various time points during the 12-month treatment period. The correlations between the choroidal vascular patterns, specifically those with or without dilated choroidal vascular channels (DCVC) revealed by ICGA, and baseline characteristics and treatment outcomes were evaluated using multiple regression models. RESULTS: The study enrolled 34 eyes of 31 patients. The average age was 59.0 ± 9.3 years, and 20 participants were men. ICGA revealed DCVCs in 21 eyes, while the remaining 13 eyes did not have DCVCs. At baseline, DCVC group was older (p = 0.03) and had a longer duration of visual symptoms (p = 0.02), with a higher vessel density (defined as the percentage of the measured area occupied by flow area) of MNV (p = 0.04), higher proportion of ellipsoid zone disruption (p = 0.01), and poorer CDVA (p = 0.03). After the 12-month treatment period, the frequency of requirement of anti-VEGF injections (p < 0.01) was higher, and the risk for CDVA <20/40 was higher (adjusted OR: 5.29, 95% CI: 1.24-22.48, p = 0.02) in eyes with DCVCs. CONCLUSIONS: For PNV, eyes with DCVCs were associated with higher vessel density of macular neovascularization and poorer CDVA at baseline, and had poorer visual and anatomical outcomes although more anti-VEGF injections were given.

Double-Needle Haptic Repositioning: A Troubleshooting Technique for Flanged Intraocular Lens Fixation.

PURPOSE: Haptic repositioning during flanged intraocular lens (IOL) fixation can be difficult, and the haptic requiring repositioning may be at increased risk of excessive bending or breakage. This study aimed to report double-needle haptic repositioning technique outcomes for the aforementioned difficulty during flanged IOL fixation. METHODS: This retrospective case series included seven eyes requiring haptic repositioning during flanged IOL fixation. The method features reinsertion of an already externalized haptic into the needle lumen followed by a needle-haptic complex internalized through the original tract into the eyeball. Thus, an adequate configuration for contralateral haptic can be achieved for insertion into the needle lumen to create a double-needle condition before both haptics are successfully externalized. RESULTS: The median follow-up duration was 24 months (range, 4-24 months). Postoperatively, the IOL was well-centered, and corrected distance visual acuity improved from 20/320 (20/4,000-20/70) to 20/50 (20/250-20/20). No intraoperative or postoperative complications were noted. CONCLUSION: The technique produced encouraging results in patients undergoing haptic repositioning during flanged IOL fixation. This technique could potentially reduce haptic overbending risk and facilitate haptic adjustment. Further studies are needed to confirm the feasibility of the technique.

Vitreoretinal surgery in the management of infectious and non-infectious uveitis - a narrative review.

PURPOSE: This study aims to conduct a narrative review about the current role of vitreoretinal surgery in the management of infectious and non-infectious uveitis. METHODS: This review was performed based on a search of the PubMed database or on relevant published papers according to our current knowledge. RESULTS: A total of 91 articles were identified in the literature review. With the advance of microincision vitrectomy surgery (MIVS), pars plana vitrectomy (PPV) has gained increasing popularity in the management of infectious and non-infectious uveitis. For diagnostic purposes, larger amounts of sample can be obtained by MIVS than traditional vitreous aspiration using needles. For treatment purposes, PPV removes vitreous opacities, decreases inflammatory cytokines and mediators of inflammation, and tackles related complications, including hypotony, epiretinal membrane, macular holes, and retinal detachment. Achieving optimum control of inflammation prior to surgery is important for surgical interventions for non-emergent therapeutic indications and complications of uveitis. Peri-operative inflammation management is essential for decreasing the risk of surgical intervention. An overall complication rate of 42-54% was reported with cataract to be the leading cause of complications. CONCLUSION: Most reports affirm the role of PPV in the management of infectious and non-infectious uveitis, although the quality of data remains limited by a lack of applying standardized reporting outcomes, limitations in study design, and a paucity of prospective data.

Overweight and Obesity as Risk Factors for Recurrent Herpetic Stromal Keratitis during Long-Term Antiviral Prophylaxis.

Although past research has shown an association between obesity and herpes simplex virus infection, the relationship between body mass index (BMI) and herpetic stromal keratitis (HSK) recurrence has never been investigated. In this study, we included HSK patients who received oral valacyclovir as prophylactic treatment between January 2016 and January 2021. Recurrence, possible risk factors, and the time to recurrence were recorded during follow-ups. Among the 56 patients included in this study, recurrence was reported in 21 (37.5%) patients. The age at disease onset and mean follow-up time were not significantly different in the recurrence and non-recurrence groups. However, in the Cox regression analysis, BMI ≥ 24 kg/m2 was noted as the variable having significant correlation with recurrence (p = 0.01 in univariate analysis and p = 0.001 in multivariate analysis). In conclusion, overweight and obesity were revealed as risk factors for HSK recurrence in patients receiving long-term antiviral prophylaxis. Further studies are needed to determine the appropriate acyclovir concentrations in the blood or aqueous humour in order to achieve desirable prophylactic effects, especially in the overweight and obese patients.

Eyelid and scleral thermal injury following phacoemulsification in silicone oil: a case report.

BACKGROUND: Phacoemulsification has been the mainstay method for extracapsular cataract extraction surgery in the anterior segment; for cases of posterior drop of lens fragments into the vitreous, a posterior segment phacoemulsification instrument (fragmatome; Alcon, Inc., Fort Worth, TX) can be employed to remove the dislocated lens materials. Studies have reported on thermal injury to the cornea during phacmoemulsification of the anterior segment. However, few studies have investigated thermal burn in the simultaneous sclera and eyelid induced by the fragmatome. Currently, there is no reports and lack of optimal strategy for the management of nucleus drop in a vitreous cavity filled with silicon oil. CASE PRESENTATION: We present the case of a 53-year-old male patient with a thermal burn wound on the upper eyelid and sclera following phacoemulsification for a dropped lens in a silicone oil-filled vitreous. We further designed an experiment to verify our hypothesis that thermal injury could be induced by the high temperature of the metal tip during phacoemulsification in silicone oil. In our experiment, during 420 s of continuous ultrasonic wave, the temperature of the fragmatome tip in the balanced salt solution (BSS) increased from 22.0 to 24.0 ºC, while the temperature of the fragmatome tip in the silicone oil group increased from 22.0 to 43.0 ºC. CONCLUSIONS: The temperature of the fragmatome tip increased significantly in silicone oil compared to BSS in the experiment. Thus, physicians should be aware of possible thermal complications when using fragmatome in eyes filled with silicone oil.

Comparative anatomical outcomes of high-flow vs. low-flow phacoemulsification cataract surgery: A systematic review and meta-analysis.

Background: Phacoemulsification is an effective and widely performed technique in cataract surgery, but the comparative anatomical outcomes, including endothelial cell loss (ECL), central corneal thickness (CCT), and central macular thickness (CMT), between high-flow and low-flow phacoemulsification cataract surgery remain unclear. Methods: This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Random-effects models were applied to measure pooled mean differences (MD) with 95% confidence intervals (CI) of anatomical outcomes between high-flow and low-flow phacoemulsification cataract surgery. We judged overall certainty of evidence (CoE) based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Results: We included six randomized controlled trials (RCTs) totaling 477 participants. The meta-analysis showed similar changes associated with these two surgery types in both ECL at postoperative days 2-14 (MD: -1.63%; 95% CI: -3.73 to 0.47%; CoE: very low), days 15-42 (MD: -0.65%; 95% CI -2.96 to 1.65%; CoE: very low) and day 43 to month 18 (MD: -0.35%; 95% CI: -1.48 to 0.78%; CoE: very low), and CCT at postoperative day 1 (MD: -16.37 µm; 95% CI: -56.91 to 24.17 µm; CoE: very low), days 2-14 (MD: -10.92 µm; 95% CI: -30.00 to 8.16 µm; CoE: very low) and days 15-42 (MD: -2.76 µm; 95% CI: -5.75 to 0.24 µm; CoE: low). By contrast, low-flow phacoemulsification showed less increase in CMT at postoperative days 15-42 (MD, -4.58 µm; 95% CI: -6.3 to -2.86 µm; CoE: low). Conclusions: We found similar anatomical outcomes, except in CMT, for both high-flow and low-flow phacoemulsification cataract surgery. Future head-to-head RCTs on visual outcomes should confirm our findings. Systematic review registration: PROSPERO, identifier: CRD42022297036.

Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs Glucagonlike Peptide-1 Receptor Agonists and Incidence of Dry Eye Disease in Patients With Type 2 Diabetes in Taiwan.

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to improve low-grade systemic and tissue inflammation; however, the association between SGLT2 inhibitor use and the incidence of dry eye disease (DED) has not been explored. Objective: To investigate the association between SGLT2 inhibitor use and dry eye disease in patients with type 2 diabetes (T2D). Design, Setting, and Participants: A retrospective cohort analysis of the largest multi-institutional electronic medical records database in Taiwan was conducted to identify patients with T2D newly receiving SGLT2 inhibitors or glucagonlike peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Data analysis was performed from March 1 to May 31, 2022. Propensity scores with inverse probability of treatment weighting were generated to enable homogeneous comparisons between the 2 groups. Exposures: Treatment with SGLT2 inhibitors or GLP-1 RAs. Main Outcomes and Measures: Incident dry eye disease, which was defined by clinical diagnoses, plus the related drug prescription. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for the risk of DED. Results: A total of 10 038 and 1077 T2D patients newly receiving SGLT2 inhibitors (mean [SD] age, 59.5 [12.1] years; 5689 [56.7%] men) or GLP-1 RAs (mean [SD] age, 58.5 [41.2] years; 587 [54.5%] men), respectively, were included in the analysis. The incidence of DED was lower in patients newly receiving SGLT2 inhibitors (9.0 events per 1000 person-years) compared with those receiving GLP-1 RAs (11.5 events per 1000 person-years), yielding a hazard ratio of 0.78 (95% CI, 0.68-0.89). Subgroup analyses indicated that the lowered DED risks associated with SGLT2 inhibitors in patients with T2D were similar across different age, sex, blood glucose level, and kidney function groups. Results from the sensitivity analyses (including the propensity score-matching approach, on-treatment analyses, and different follow-up periods of 1, 2, and 3 years) were similar to the main analyses. Conclusions and Relevance: The findings of this study suggest that patients with T2D newly receiving SGLT2 inhibitors may have a lower risk for DED compared with those receiving GLP-1 RAs. Prospective studies are needed to analyze these results.

Long-Term Outcome of Treatment with 2% Topical Ganciclovir Solution in Cytomegalovirus Anterior Uveitis and Corneal Endotheliitis.

Purpose: This study aimed to evaluate the therapeutic efficacy and long-term outcomes of treatment with topical 2% ganciclovir solution in immunocompetent patients with aqueous humor polymerase chain reaction (PCR)-proven cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis. Methods: We retrospectively reviewed the findings for immunocompetent patients diagnosed with CMV uveitis or endotheliitis based on clinical manifestations and polymerase chain reaction (PCR) examination results and treated with topical 2% ganciclovir solution at National Cheng Kung University Hospital. Clinical outcome measurements included evaluations of the response rate, relapses, resolution of anterior chamber inflammation, visual acuity, and intraocular pressure. Results: The study included 38 eyes of 32 patients. Long-term administration of topical 2% ganciclovir significantly decreased keratic precipitates (p = 0.001), anterior chamber cells (p = 0.001), and reduced intraocular pressure (p < 0.001). Only one eye was unresponsive to topical ganciclovir treatment, and the recurrence decreased to 0.13 relapses per year. The presence of keratic precipitates and higher intraocular pressure at the initial presentation were significantly associated with recurrence (p = 0.036 and p = 0.001, respectively). Conclusions: Long-term use of topical 2% ganciclovir solution is effective, safe, and applicable when commercialized ganciclovir gel is not available.

A systematic approach to reduce intraocular pressure for the treatment of glaucoma.

Glaucoma is the leading cause of irreversible blindness due to increased intraocular pressure (IOP) in the eye. We have developed a novel treatment option for glaucoma based on a real-time IOP-dependent nitric oxide synthase (NOS) and packed in a therapeutic contact lens to reduce the IOP. First, 1.6 nmole nitric oxide was produced from the genetic chassis, which was optimized for isopropyl ß-d-1-thiogalactopyranoside (IPTG) induction in a T7 expression system. For biosafety concerns to human being, the csgAD genes responsible for curli biofilm formation in Escherichia coli were co-expressed with NOS in the designated NOSAD strain to strengthen the adherence of cells to the contact lens, thereby preventing the contamination into the eyes. Moreover, NOSAD is a diaminopimelic acid (DAP) auxotrophic strain, which cannot survive without supplementation of DAP and reached the critical consideration of biosafety to the environment. We also demonstrated that the nitric oxide diffusion was 3.6-times enhanced from penetration into the aqueous humor of porcine eyes. The deformation ratio of the contact lens was correlated to the change of IOP by using a digital image correlation (DIC) system in a porcine eye model. The novel systematic approach provides an alternative treatment for glaucoma patients in the future.

Risk of dialysis in patients receiving intravitreal anti-vascular endothelial growth factor treatment: a population-based cohort study.

We utilized the Longitudinal Health Insurance Database which was stemmed from the Taiwan's National Health Insurance Research Database to conduct a retrospective cohort study investigating the risk of becoming dialysis dependent after receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents for retinal diseases. Patients newly receiving intravitreal ranibizumab or aflibercept from 2000 to 2017 for age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, retinal vein occlusions, or myopic choroid neovascularization were included as the study group, and patients with same retinal diseases but did not receive intravitreal anti-VEGFs served as controls extracted by age- and sex-matched (1:4) and further propensity score matching (PSM). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the risk of dialysis. A cohort of 2447 anti-VEGF users and 2447 controls by PSM were evaluated. Higher dialysis risks were observed among patients newly receiving anti-VEGF agents compared to controls (adjusted HR: 1.849; 95% CI: 1.378-2.482) in the PSM cohort. For subgroup analysis, patients newly receiving anti-VEGF treatment for diabetic macular edema had significant risk (adjusted HR: 1.834; 95% CI: 1.448-2.324) of becoming dialysis-dependent, while patients in other subgroups demonstrated similar risks as the controls. In conclusion, intravitreal anti-VEGF agents might increase the risk of becoming dialysis-dependent, especially in patients who are treated for diabetic macular edema.

Oral short-chain fatty acids administration regulates innate anxiety in adult microbiome-depleted mice.

Anxiety is characterized by feelings of tension and worry even in the absence of threatening stimulus. Pathological condition of anxiety elicits defensive behavior and aversive reaction ultimately impacting individuals and society. The gut microbiota has been shown to contribute to the modulation of anxiety-like behavior in rodents through the gut-brain axis. Several studies observed that germ-free (GF) and the broad spectrum of antibiotic cocktail (ABX)-treated rodents display lowered anxiety-like behavior. We speculate that gut microbial short-chain fatty acids (SCFA) modulate the innate anxiety response. Herein, we administered SCFA in the drinking water in adult mice treated with ABX to deplete the microbiota and tested their anxiety-like behavior. To further augment the innate fear response, we enhanced the aversive stimulus of the anxiety-like behavior tests. Strikingly, we found that the anxiety-like behavior in ABX mice was not altered when enhanced aversive stimulus, while control and ABX mice supplemented with SCFA displayed increased anxiety-like behavior. Vagus nerve serves as a promising signaling pathway in the gut-brain axis. We determined the role of vagus nerve by subdiaphragmatic vagotomy (SDV) in ABX mice supplemented with SCFA. We found that the restored anxiety-like behavior in ABX mice by SCFA was unaffected by SDV. These findings suggest that gut microbiota can regulate anxiety-like behavior through their fermentation products SCFA.